It is estimated that more than 371 new biotechnology-based medicines are in the industry pipeline. Such biotechnology-based medicines include therapeutic proteins such as enzymes, soluble receptors, ligands, blood proteins, and monoclonal antibodies. Protein-based therapy, especially monoclonal antibody-based therapy, has become an important method for treating diseases such as cancer, allergic diseases, asthma, and organ transplantation. At the end of 2003 fourteen antibody-based therapies had been approved by the Food and Drug Administration to treat different human diseases.
Antibody-based therapy is usually administered on a regular basis and requires several mg/kg dosing by injection. Subcutaneous injection is a typical route of administration of these therapies. Because of the small volumes used for subcutaneous injection (usually 1.0 mL-1.2 mL), for high dose antibody therapies, this route of administration requires high concentration protein formulations (e.g., 50 mg/ml-300 mg/ml).
High protein concentrations pose challenges relating to the physical and chemical stability of the protein, and difficulty with manufacture, storage, and delivery of the protein formulation. One problem is the tendency of proteins to form particulates during processing and/or storage, which make manipulation during further processing difficult. To attempt to obviate this problem, surfactants and/or sugars have been added to protein formulations. Although surfactants and sugars may reduce the degree of particulate formation of proteins, they do not address another problem associated with manipulating and administering concentrated protein formulations, i.e., increased viscosity. In fact, sugars may enhance the intermolecular interactions within a protein or between proteins and increase the viscosity of the protein formulation.
Increased viscosity of protein formulations has negative ramifications from processing through drug delivery to the patient. Accordingly, there is a need in the art to develop relatively high concentration protein formulations with suitably low viscosities that are suitable for manufacture, storage, and administration.